The Frank-Starling Curve in heart muscle indicates the relationship between resting length (or tension) and stroke work (or developed tension), and it describes one of the two major mechanisms by which the intact heart can acutely vary its performance. The cellular basis for this relationship is not known although several laboratories have proposed that it is produced by the nature of the alignment of the contractile filaments. In this project the influence of contractile filament alignment on the performance of an isolated bundle of cardiac muscle and the effect of length on the excitation-contraction coupling system of isolated heart muscle will be studied. The striation pattern and the tension of an isolated living bundle of heart muscle will be monitored continuously during periods of rest and mechanical activity at different sarcomere lengths. The ultrastructure of the filaments and the sarcoplasmic reticulum at different sarcomere lengths will be studied with the electron microscope. Studies with a preparation of isolated heart in which the membrane permeability has been increased by treatment with EDTA will be continued to determine the intracellular structures that bind calcium. The affinities and capacities of these structures for calcium as well as the mechanisms for its release will be investigated. BIBLIOGRAPHIC REFERENCES: S. Winegrad, G. McClellan, T. Robinson and N. Lai. Length dependent interactions between thick and thin filaments in the resting state in cardiac muscle. European J. Cardiology, in press. S. Winegard. Control of resting and contracted length of cardiac cells by internal loads. Biophys. J. 15:152, 1975.